Ventilation scintigraphy and inhalation scintigraphy are two known scintigraphic methods for measuring regional pulmonary ventilation. They are particularly useful in diagnosing medical conditions such as pulmonary embolism, bronchial carcinoma and chronic obstructive pulmonary disease. In both methods, the patient inhales radioactive gases, for example krypton or xenon, or particles which have been labelled with radioactive particles. The radioactivity in the lungs is then measured with a gamma camera, a scanner or some other similarly suitable detector and is subsequently evaluated.
The use of krypton or xenon gases, as disclosed in U.S. Pat. Nos. 3,881,463 to LeMon and 4,706,683 to Chilton et al., suffers from numerous disadvantages. For instance, the relatively short half-lives (about 15-30 seconds) of xenon and krypton require that the scan be performed very shortly after administration of the gas. Therefore, it is more likely that additional administrations will be necessary if the scan needs to be repeated. Furthermore, methods of ventilation scintigraphy utilizing these radioactive gases suffer from the drawback that xenon and krypton are very scarce and hence expensive, as well as being subject to other difficulties in their administration.
The generation of an aerosol having monodisperse particles, i.e. particles of a relatively uniform size, less than 2 microns in diameter has proven to be critical to the diagnostic value of ventilation scintigraphy according to George V. Taplin in his article "Lung perfusion-inhalation, scintigraphy in obstructive airway disease and pulmonary embolism" Radiologic Clinics of North America, Vol. XVI., No. 3, December 1978. Taplin explains that if a large proportion of the particles in a scintigraphy aerosol exceed 2 microns in diameter, then undesireable tracheal and bronchial hyperdeposition of the aerosol occurs, i.e., the radioactive particles do not penetrate the lungs sufficiently to give diagnostically useful images.
The two major types of methods for generating respiratory aerosols which are known in the prior art are compressed air nebulization and ultrasound nebulization. The known methods have proven to be inconsistent for producing scintigraphy aerosols which meet the criterion established in the Taplin article.
Aerosol generation devices based on compressed air nebulization methods are disclosed in U.S. Pat. Nos. 4,510,929 to Gordoni et al., 4,660,547 to Kremer et al., 4,741,331 to Wunderlich, 4,782,828 to Burnett et al. and 4,803,977 to Kremer. As a representative example, U.S. Pat. No 4,660,547 to Kremer, et al. discloses aerosol generation by means of a compressed air system which utilizes to rather cumbersome radiation safety controls and procedures. The alternative source of compressed air, i.e. the hospital's own compressed air system, suffers from the disadvantage that the pressure generated thereby is usually subject to wide variation and therefore cannot provide the monodispersity required for accurate ventilation scintigraphy. Furthermore, compressed air aerosol generating systems may suffer from the disadvantage that the aerosol is forced into the patient's trachea, rather than being inhaled, possibly increasing the hyperdeposition of the radioactive aerosol in the airway instead of the bronchioles and the lungs.
A second method for generating an aerosol is by means of ultrasound. The devices disclosed in U.S. Pat. No. 3,774,602 to Edwards and German Patent No. 1,813,776 to Bahr et al. use an ultrasonic generator for producing aerosols adapted specifically for use in inhalation therapy and, therefore, the droplets produced thereby can be up to 6 microns in size (i.e. a size which greatly exceeds the recommended size of 2 microns). U.S. Pat. No. 4,094,317 to Wasnich discloses an example of an ultrasound nebulization system intended for use in inhalation scintigraphy in which the radioactively-labelled substance is contained at the bottom of a nebulizing chamber. The nebulizing chamber is surrounded by an ultrasound-conducting medium received in a container, at the bottom of which rests an ultrasonic generator. The droplets of the aerosol generated by this system vary greatly in size and the nebulizing chamber is actually designed to produce droplets in a size range of about 0.5 microns to about 3.5 microns. An impaction sphere is provided to trap droplets whose diameter exceeds 3.5 microns, causing the droplets to condense and recollect at the bottom of the nebulizing chamber where they are reatomized. A disadvantage of this system is that many of the particles allowed to pass are still larger than 2 microns which, as previously noted, is the maximum size preferred for effective diagnosis.
An additional problem is encountered when using ultrasound nebulization systems. Specifically, it has been found that the ultrasonic energy tends to disrupt the bond between most carrier media and the label. This disruption results in an undesirable amount of free radioactive labels leading to false clinical results. Therefore, choosing a suitable carrier medium and label itself has proven to be a significant problem.
There are no other methods known in the prior art which will ensure the production of an aerosol in which a high proportion of the aerosol particles are 2 microns or less in size. The possibility of using filters designed to prevent the passage and inhalation of particles larger than 2 microns is impractical because of the considerable air-flow restrictions imposed by such filters. An air-resistance which is too high must be avoided because most patients with severe lung damage, for whom scintigraphic investigations are of particular importance, are unable to inhale the aerosol to an extent adequate for accurate diagnoses.
The prior art systems also encounter difficulties in delivering a sufficient amount of the radioactive label to the lungs without exposing operators to large doses of radiation. For instance, the method disclosed in the Wasnich patent requires the injection of 20-30 mCi of .sup.99m technetiumphytate (.sup.99m Tc-phytate) in a 0.5 ml dose into the nebulizer for use in inhalation scintigraphy. Of that dose, only about 0.5 mCi actually penetrates the lungs. This relatively low yield makes tapping a fresh source of .sup.99m Tc-phytate necessary, thereby increasing the cost of the test as well as the risk of radiation exposure to the technician. The situation is further aggravated by the fact that many of the labelled particles are too large to be useful.
The methods disclosed in at least some of the prior art patents discussed above have a further disadvantage in that they require extreme care in handling the radioactive substances or they do not provide adequate protection against radiation exposure for the technician. For example, the device disclosed in the Wasnich patent is unshielded. Combined with the relatively high doses of .sup.99m Tc-phytate required, the lack of adequate shielding together with the need for multiple doses make it likely that a technician could only administer the scintigraphy a small number of times before exceeding recommended radiation exposure levels.